A number of organic acid platinum (II) complexes wherein the ligand component is 1,2-diaminocyclohexane have been reported. However, many of them have low solubility so that they cannot be intravenously administered (e.g., cyclobutane-1,1-dicarboxylate disclosed in Japanese Laid Open Patent Application (Kokai) No. 60-10952) while the intravenous administration is the administration route of platinum complexes or, in the alternative, their stabilities in aqueous solutions are low although their solubilities are large (e.g., trimellitate disclosed by P. J. Andrulis et al., Proceedings of the Fifth International Symposium and Other Metal Compounds in Cancer Chemotherapy, p.450 (1987)).
On the other hand, there is a problem in seeking a platinum complex with anti-tumor activity that an impurity contaminated in the synthesized platinum complex often shows anti-tumor activity. Therefore, it is necessary to appropriately purify the platinum complex. Recently, James D. Hoeschele and N. Farrel reported examples wherein the anti-tumor activity of a platinum complex disappeared after an appropriate purification of the platinum complex in Inorg. Chem., 27, 4106-4113 (1988). That is, they reported that among the 1,2-diaminocyclohexane Pt(II) complexes which were reported to be water-soluble and to have high anti-tumor activities, some complexes lost their anti-tumor activities after purification. Thus, they emphasized the importance of obtaining a sample with a high purity for the evaluation of the anti-tumor activities.
The present inventors previously discovered that the platinum (II) complexes containing 1 mole of 1,2-diaminocyclohexane and 2 moles of 3-acetyl-6-methyltetrahydropyran-2,4-dione or its analogue have anti-tumor activities (EP 337,459). However, it turned out that these complexes do not show anti-tumor activities when they are highly purified. Thus, it is important for an industrial preparation that the synthesized complex can be purified easily and the complex with a high purity can be obtained easily.
The object of the present invention is to provide a novel platinum (II) complex with a strong anti-tumor activity, which may easily be purified, which has a solubility that enables intravenous administration, and which is stable in aqueous solution.